Introduction Lung transplantation in the presence of donor specific antibodies (DSA) is safe with peri-operative desensitization, although persistence of DSA is common. Herein, we present a unique case of a highly sensitized lung transplant recipient with selective loss of DSA post-transplantation. Case Report A 65-year-old female with a calculated PRA (cPRA) value of of 17% (class I) and 100% (class II), underwent bilateral lung transplantation for chronic obstructive pulmonary disease. Virtual crossmatch (VCM) was positive, involving DPB1*04:01, DR17, and DR52. The subsequent flow cytometry B-cell crossmatch was strongly positive (median channel shift 296). She received peri-operative desensitization protocol for VCM positive patients, which includes intra-operative and post-operative plasmapheresis, intravenous immune globulin, and anti-thymocyte globulin. Maintenance immunosuppression included cyclosporine (target trough 250-350 umol/L), mycophenolic acid 900mg BID and prednisone 20 mg OD. An increase in DSA reactivity was observed one month after transplant (DPB1*04:01 (MFI=17639), DR17 (MFI=17812), and DR52 (MFI=19414). Repeat HLA testing at 3, 4, and 6 months post-transplant showed sequential reduction of DSAs to below the laboratory cut-off for positivity point despite persistence of non-DSA alloantibodies. The patient continues to maintain good lung function with an FEV1 of 2L (86% of predicted) at 6 months post-transplant. Surveillance transbronchial biopsies at 3 and 6 months were free of cellular rejection. Summary Despite initial rebound of pre-formed DSA following peri-operative desensitization, sustained selective clearance of the DSA subsequently occurred in this case, which likely benefited graft function. Similar cases have been reported after combined kidney-liver transplant. Robust laboratory research and prospective studies are required to understand the mechanism of selective DSA elimination in organ transplantation.

Waiting list mortality for lung transplantation is 15-25%, while only 20% of lungs from multiorgan donors are deemed suitable for transplantation. Ex vivo lung perfusion (EVLP) is a technique to increase the donor pool by reassessing and reconditioning extended criteria donor lungs (ED) that would otherwise be rejected. Previous studies have shown non-inferior short- and mid-term outcomes in EVLP lung transplantation using these lungs. Here, we report the long-term follow-up of our EVLP recipients.

Bronchial complications requiring intervention have been reported in 9 to 13% of lung transplant (LTx) recipients. We sought to assess the incidence and risk factors of bronchial complications in a large single center cohort.

Lung transplantation is offered at only four centres in Canada. The Toronto Lung Transplant Program has used Telehealth, a secure two-way videoconferencing system, to improve access to consultations for transplant. Mortality differences and transplant candidacy outcomes in patients seen in-person vs. via Telehealth were examined to ensure that Telehealth is not inferior to conventional visits.

CMV seronegative recipients receiving a seropositive allograft (D+/R-) are at a high risk of developing CMV disease. Our program increased the duration of CMV prophylaxis from 6 to 9 months in high risk patients from May 2013 onwards. Here, we present the impact of the change in our protocol on the incidence of CMV infection, disease, and side effects.

Background Although molecular testing has become standard in managing advanced nonsquamous non-small-cell lung cancer (NSCLC), most patients undergo minimally invasive procedures, and the diagnostic tumour specimens available for testing are usually limited. A knowledge translation initiative to educate diagnostic specialists about sampling techniques and laboratory processes was undertaken to improve the uptake and application of molecular testing in advanced lung cancer.Methods A multidisciplinary panel of physician experts including pathologists, respirologists, interventional thoracic radiologists, thoracic surgeons, medical oncologists, and radiation oncologists developed a specialty-specific education program, adapting international clinical guidelines to the local Ontario context. Expert recommendations from the program are reported here.Results Panel experts agreed that specialists procuring samples for lung cancer diagnosis should choose biopsy techniques that maximize tumour cellularity, and that conservation strategies to maximize tissue for molecular testing should be used in tissue processing. The timeliness of molecular reporting can be improved by pathologist-initiated reflex testing upon confirmation of nonsquamous NSCLC and by prompt transportation of specimens to designated molecular diagnostic centres. To coordinate timely molecular testing and optimal treatment, collaboration and communication between all clinicians involved in diagnosing patients with advanced lung cancer are mandatory.Conclusions Knowledge transfer to diagnostic lung cancer specialists could potentially improve molecular testing and treatment for advanced lung cancer patients.

Donor‐specific HLA antibodies (DSA) have an adverse effect on short‐term and long‐term lung transplant outcomes. We implemented a perioperative strategy to treat DSA‐positive recipients, leading to equivalent rejection and graft survival outcomes. Pretransplant DSA were identified to HLA‐A, B, C, DR and DQ antigens. DSA‐positive patients were transplanted if panel reactive antibody (PRA) ≥30% or medically urgent and desensitized with perioperative plasma exchange, intravenous immune globulin, antithymocyte globulin (ATG), and mycophenolic acid (MPA). PRA‐positive/DSA‐negative recipients received MPA. Unsensitized patients received routine cyclosporine, azathioprine and prednisone without ATG. From 2008–2011, 340 lung‐only first transplants were performed: 53 DSA‐positive, 93 PRA‐positive/DSA‐negative and 194 unsensitized. Thirty‐day survival was 96 %/99%/96% in the three groups, respectively. One‐year graft survival was 89%/88%/86% (p = 0.47). DSA‐positive and PRA‐positive/DSA‐negative patients were less likely to experience any ≥ grade 2 acute rejection (9% and 9% vs. 18% unsensitized p = 0.04). Maximum predicted forced expiratory volume (1 s) (81%/74%/76%, p = NS) and predicted forced vital capacity (81%/77%/78%, respectively, p = NS) were equivalent between groups. With the application of this perioperative treatment protocol, lung transplantation can be safely performed in DSA/PRA‐positive patients, with similar outcomes to unsensitized recipients.

Chronic lung allograft dysfunction (CLAD) remains a major cause of morbidity and mortality after transplantation. Our recent work suggested that neutrophils may play important role in the development of restrictive allograft syndrome (RAS), a subtype of CLAD. We aimed to further characterize human CLAD subtypes by profiling neutrophilic enzymes in bronchoalveolar lavage fluid (BALF). 27 consecutively identified specimens from patients with CLAD (9 RAS, 18 bronchiolitis obliterans syndrome (BOS) ) and 24 controls from patients with no CLAD were included. All the BALF specimens from CLAD cases were taken after their clinical onset. CLAD and its subtypes were defined based on pulmonary function test results. Neutrophilic elastase and matrix metalloproteinase (MMP)-8 expression were measured in BALF by enzyme-linked immunosorbent assay. Both neutrophilic elastase and MMP-8 were upregulated in RAS compared to controls (p< 0.0001 and p< 0.001, respectively) and upregulated in BOS compared to controls (p< 0.01 and p< 0.01, respectively). Moreover, neutrophilic elastase was upregulated in RAS compared to BOS (median 111.0 vs. 25.2 ng/mL, p< 0.05), whereas MMP-8 did not show significant difference between RAS and BOS (median 3.7 vs 1.6 ng/mL, p= 0.153). In CLAD patients, neutrophilic elastase and MMP-8 were upregulated in both RAS and BOS. Importantly, we have noted further upregulation of neutrophilic elastase in RAS. Hopefully, further characterization of molecular pathways involved in the development of CLAD subtypes will help to develop more accurate diagnostics and ultimately specifically directed therapies.

The long-term success of lung transplantation is limited by chronic lung allograft dysfunction (CLAD). The purpose of this study was to investigate the alveolar alarmin profiles in CLAD subtypes, restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS). Bronchoalveolar lavage (BAL) samples were collected from 53 recipients who underwent double lung or heart-lung transplantation, including patients with RAS (n = 10), BOS (n = 18) and No CLAD (n = 25). Protein levels of alarmins such as S100A8, S100A9, S100A8/A9, S100A12, S100P, high-mobility group box 1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in BAL fluid were measured. RAS and BOS showed higher expressions of S100A8, S100A8/A9 and S100A12 compared with No CLAD (p < 0.0001, p < 0.0001, p < 0.0001 in RAS vs. No CLAD, p = 0.0006, p = 0.0044, p = 0.0086 in BOS vs. No CLAD, respectively). Moreover, RAS showed greater up-regulation of S100A9, S100A8/A9, S100A12, S100P and HMGB1 compared with BOS (p = 0.0094, p = 0.038, p = 0.041, p = 0.035 and p = 0.010, respectively). sRAGE did not show significant difference among the three groups (p = 0.174). Our results demonstrate distinct expression patterns of alveolar alarmins in RAS and BOS, suggesting that RAS and BOS may represent biologically different subtypes. Further refinements in biologic profiling will lead to a better understanding of CLAD.

PurposeAs the population of transplanted patients grows, so does the demand for retransplantation. Lung retransplantation is feasible in select patients, but survival has been inferior compared to initial transplants. Studies of retransplant recipients have generally focused on graft function and survival. Our objective was to perform a detailed analysis of this patient group, including novel variables such as functional status, renal function, HLA antibodies and quality of life.MethodsA retrospective review was performed of patients (n=38) retransplanted in our program between 06/2001 and 08/2013. Variables assessed are outlined in Table 1. We compared best quality of life measurements after the first and second transplants. We used Kaplan-Meier curves with log-rank tests to assess survival and paired t tests for within-patient comparison.ResultsMean age at retransplant was 37y (range 19-60) and median time from first transplant was 54.5 months (0.5-266). Mean preoperative 6MWD was 339m (SD 143). Indications for retransplant were: 36 BOS (94.8), 1 primary graft failure (2.6), 1 recurrent BAC. Median follow up duration was 15.5 months (2-148). Outcomes are detailed in Table 1. DSA post retransplant was present in 12 of 25 (48%) patients with available data. Quality of life scores were similar when compared with initial transplant for either SF-36 (p=0.7) or SGRQ (p=0.9). Survival is shown in Figure 1. Median survival was 4.0 years.ConclusionLung retransplantation is more challenging than first time transplantation. Despite this, our results show that with experience, acceptable clinical, functional and quality of life outcomes are achievable in carefully selected patients.FigView Large Image Figure ViewerDownload Hi-res image Download (PPT) PurposeAs the population of transplanted patients grows, so does the demand for retransplantation. Lung retransplantation is feasible in select patients, but survival has been inferior compared to initial transplants. Studies of retransplant recipients have generally focused on graft function and survival. Our objective was to perform a detailed analysis of this patient group, including novel variables such as functional status, renal function, HLA antibodies and quality of life. As the population of transplanted patients grows, so does the demand for retransplantation. Lung retransplantation is feasible in select patients, but survival has been inferior compared to initial transplants. Studies of retransplant recipients have generally focused on graft function and survival. Our objective was to perform a detailed analysis of this patient group, including novel variables such as functional status, renal function, HLA antibodies and quality of life. MethodsA retrospective review was performed of patients (n=38) retransplanted in our program between 06/2001 and 08/2013. Variables assessed are outlined in Table 1. We compared best quality of life measurements after the first and second transplants. We used Kaplan-Meier curves with log-rank tests to assess survival and paired t tests for within-patient comparison. A retrospective review was performed of patients (n=38) retransplanted in our program between 06/2001 and 08/2013. Variables assessed are outlined in Table 1. We compared best quality of life measurements after the first and second transplants. We used Kaplan-Meier curves with log-rank tests to assess survival and paired t tests for within-patient comparison. ResultsMean age at retransplant was 37y (range 19-60) and median time from first transplant was 54.5 months (0.5-266). Mean preoperative 6MWD was 339m (SD 143). Indications for retransplant were: 36 BOS (94.8), 1 primary graft failure (2.6), 1 recurrent BAC. Median follow up duration was 15.5 months (2-148). Outcomes are detailed in Table 1. DSA post retransplant was present in 12 of 25 (48%) patients with available data. Quality of life scores were similar when compared with initial transplant for either SF-36 (p=0.7) or SGRQ (p=0.9). Survival is shown in Figure 1. Median survival was 4.0 years. Mean age at retransplant was 37y (range 19-60) and median time from first transplant was 54.5 months (0.5-266). Mean preoperative 6MWD was 339m (SD 143). Indications for retransplant were: 36 BOS (94.8), 1 primary graft failure (2.6), 1 recurrent BAC. Median follow up duration was 15.5 months (2-148). Outcomes are detailed in Table 1. DSA post retransplant was present in 12 of 25 (48%) patients with available data. Quality of life scores were similar when compared with initial transplant for either SF-36 (p=0.7) or SGRQ (p=0.9). Survival is shown in Figure 1. Median survival was 4.0 years. ConclusionLung retransplantation is more challenging than first time transplantation. Despite this, our results show that with experience, acceptable clinical, functional and quality of life outcomes are achievable in carefully selected patients. Lung retransplantation is more challenging than first time transplantation. Despite this, our results show that with experience, acceptable clinical, functional and quality of life outcomes are achievable in carefully selected patients.

The median survival for patients with cystic fibrosis(CF) continues to improve and lung transplantation (LTx) has contibuted significantly to the treatment of patients with end stage CF lung disease. This study reports on the largest single-center experience of outcomes in LTx in both pediatric and adult CF patients.

PurposeHLA antibodies and DSA are historically associated with decreased lung allograft survival and rejection, and are a barrier to lung transplant. Few results of interventions have been reported. We report the success of a perioperative desensitization protocol for sensitized lung recipients.Methods and MaterialsRecipients were tested for DSA at HLA A, B, C, DR and DQ. DSA+ patients were transplanted if PRA≥30% or high medical urgency and were desensitized with perioperative plasma exchange, intravenous immune globulin, antithymocyte globulin, and MMF instead of standard azathioprine(aza). Recipients with positive panel reactive antibodies (PRA+) but no DSA (DSA-) received MMF instead of aza. Routine therapy for unsensitized (PRA0) patients was cyclosporine, aza and prednisone without ATG.Results340 first lung transplants were performed 2008-11: 53 DSA+, 93 PRA+DSA-,194 PRA0. Age, diagnosis, CMV status, single vs double lung, and donor characteristics (age, smoking, PaO2, donation after cardiac death, EVLP) were similar between groups. By Ab group (DSA+ / PRA+DSA- / PRA0): Median wait time to transplant was 167/92/100d (p=0.02). More DSA+ were female (62/44/36% p=0.003), and were urgent status at transplant (85/80/67% p=0.0005) with higher mean LAS (42/39/36 p=0.02). Despite increased pre-transplant morbidity, sensitized patients were less likely to experience any ≥ grade 2 acute rejection (9/9/18% p=0.04); max %predFEV1(81/74/76), %predFVC (81/77/79) and graft survival were equivalent between groups. [figure 1]ConclusionsWith this desensitization protocol, lung transplant can be safely performed in highly sensitized recipients with similar outcomes to unsensitized recipients. HLA antibodies and DSA are historically associated with decreased lung allograft survival and rejection, and are a barrier to lung transplant. Few results of interventions have been reported. We report the success of a perioperative desensitization protocol for sensitized lung recipients. Recipients were tested for DSA at HLA A, B, C, DR and DQ. DSA+ patients were transplanted if PRA≥30% or high medical urgency and were desensitized with perioperative plasma exchange, intravenous immune globulin, antithymocyte globulin, and MMF instead of standard azathioprine(aza). Recipients with positive panel reactive antibodies (PRA+) but no DSA (DSA-) received MMF instead of aza. Routine therapy for unsensitized (PRA0) patients was cyclosporine, aza and prednisone without ATG. 340 first lung transplants were performed 2008-11: 53 DSA+, 93 PRA+DSA-,194 PRA0. Age, diagnosis, CMV status, single vs double lung, and donor characteristics (age, smoking, PaO2, donation after cardiac death, EVLP) were similar between groups. By Ab group (DSA+ / PRA+DSA- / PRA0): Median wait time to transplant was 167/92/100d (p=0.02). More DSA+ were female (62/44/36% p=0.003), and were urgent status at transplant (85/80/67% p=0.0005) with higher mean LAS (42/39/36 p=0.02). Despite increased pre-transplant morbidity, sensitized patients were less likely to experience any ≥ grade 2 acute rejection (9/9/18% p=0.04); max %predFEV1(81/74/76), %predFVC (81/77/79) and graft survival were equivalent between groups. [figure 1] With this desensitization protocol, lung transplant can be safely performed in highly sensitized recipients with similar outcomes to unsensitized recipients.

The long-term success of lung transplantation continues to be challenged by the development of chronic lung allograft dysfunction (CLAD). The purpose of this study was to investigate the relationship between cytokine expression levels in pre-implanted donor lungs and the posttransplant development of CLAD and its subtypes, bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Of 109 patients who underwent bilateral lung or heart–lung transplantation and survived for more than 3 months, 50 BOS, 21 RAS and 38 patients with No CLAD were identified by pulmonary function test results. Using donor lung tissue biopsies sampled from each patient, expression levels of IL-6, IL-1β, IL-8, IL-10, interferon-γ and tumor necrosis factor-α mRNA were measured. IL-6 expression levels were significantly higher in pre-implanted lungs of patients that ultimately developed BOS compared to RAS and No CLAD (p = 0.025 and 0.011, respectively). Cox regression analysis demonstrated an association between high IL-6 expression levels and BOS development (hazard ratio = 4.98; 95% confidence interval = 2.42–10.2, p < 0.001). In conclusion, high IL-6 mRNA expression levels in pre-implanted donor lungs were associated with the development of BOS, not RAS. This association further supports the contention that early graft injury impacts on both late graft function and early graft function.

Purpose A steady increase in the number of lung transplantations performed world-wide has led to a shortage in donor lungs. As a result, mortality on the waiting list may be as high as 30-40%. To increase the supply of donor lungs, we have developed normothermic ex-vivo lung perfusion (EVLP) to treat and repair injured donor lungs and increase the number of donor lungs. We have shown previously that the short-term results with EVLP-treated donor lungs are similar to those of the conventional donor lungs. The aim of this study was to investigate the long-term results of EVLP-donors. Methods and Materials We studied the survival, development of BOS, and other functional outcomes of lung transplant recipients of either EVLP-treated lungs or conventional donor lungs transplanted in the same center in the same time frame from September 2008 to November 2012. The whole cohort (EVLP n=56, Controls n=252) was used for survival analyses while the other analyses were made with patients that were transplanted 3 or more years ago (EVLP n=18, Controls n=91). Results As shown in Figure 1 , the survival and freedom from BOS were similar in the two groups. Also, the ratio between the highest FEV1 posttransplant and predicted FEV1 were similar (EVLP 76% ± 30% vs. control 73% ± 24%, P=NS) as was the mean change between pre- and postoperative 6-minute walking tests (EVLP 181m ± 117m vs. control 213m ± 143m, P=NS). Conclusions The recipients of EVLP-treated lung allografts have a similar survival and functional outcome to those patients receiving conventional donor lungs. This suggests that EVLP is an effective and safe method of expanding our donor pool giving us a valuable tool to increase the number of lung transplantations and reduce mortality on the waiting list.

PurposeChronic lung allograft dysfunction (CLAD) remains a major cause of mortality and morbidity after transplantation. We have noted restrictive allograft syndrome (RAS) as a novel subtype of CLAD. We aimed to further characterize human CLAD subtypes by profiling damage-associated molecular pattern molecules in bronchoalveolar lavage fluid (BALF).Methods and Materials17 consecutively identified specimens from patients with CLAD (5 RAS, 12 bronchiolitis obliterans syndrome (BOS) ) and 12 controls from patients with no CLAD were included. All the BALF specimens from CLAD cases were taken after their clinical onset. CLAD and its subtypes were defined based on pulmonary function test results. S100A8, S100A9, S100A12, S100P and high mobility group box-1 (HMGB-1) expression were measured in BALF by enzyme-linked immunosorbent assay.ResultsAll of S100A8, S100A9, S100A12 and S100P were upregulated in RAS compared to controls (p<0.005, p<0.005, p<0.01 and p<0.01, respectively), whereas HMGB-1 showed no statistically significant differences. Moreover, S100A9 was upregulated in RAS compared to BOS (median 37.5 vs. 5.1 ng/mL, p<0.05). In contrast, S100A8 was elevated in BOS compared with controls (median 58.8 vs. 19.1 ng/mL, p<0.05). Neither S100A12 or S100 showed any differences in RAS vs. BOS or in BOS vs. controls. [figure 1]ConclusionsIn CLAD patients, we have noted a distinct difference in the expression of S100 family proteins in BALF. It appears that S100A9 is associated with RAS and not BOS. Hopefully, further characterization of molecular pathways involved in the development of CLAD subtypes will help to develop more accurate diagnostics and specifically directed therapies. Chronic lung allograft dysfunction (CLAD) remains a major cause of mortality and morbidity after transplantation. We have noted restrictive allograft syndrome (RAS) as a novel subtype of CLAD. We aimed to further characterize human CLAD subtypes by profiling damage-associated molecular pattern molecules in bronchoalveolar lavage fluid (BALF). 17 consecutively identified specimens from patients with CLAD (5 RAS, 12 bronchiolitis obliterans syndrome (BOS) ) and 12 controls from patients with no CLAD were included. All the BALF specimens from CLAD cases were taken after their clinical onset. CLAD and its subtypes were defined based on pulmonary function test results. S100A8, S100A9, S100A12, S100P and high mobility group box-1 (HMGB-1) expression were measured in BALF by enzyme-linked immunosorbent assay. All of S100A8, S100A9, S100A12 and S100P were upregulated in RAS compared to controls (p<0.005, p<0.005, p<0.01 and p<0.01, respectively), whereas HMGB-1 showed no statistically significant differences. Moreover, S100A9 was upregulated in RAS compared to BOS (median 37.5 vs. 5.1 ng/mL, p<0.05). In contrast, S100A8 was elevated in BOS compared with controls (median 58.8 vs. 19.1 ng/mL, p<0.05). Neither S100A12 or S100 showed any differences in RAS vs. BOS or in BOS vs. controls. [figure 1] In CLAD patients, we have noted a distinct difference in the expression of S100 family proteins in BALF. It appears that S100A9 is associated with RAS and not BOS. Hopefully, further characterization of molecular pathways involved in the development of CLAD subtypes will help to develop more accurate diagnostics and specifically directed therapies.

Chronic lung allograft dysfunction (CLAD), predominantly represented as bronchiolitis obliterans syndrome (BOS), is a major limitation to long-term success after lung transplantation. We have defined restrictive allograft syndrome (RAS) as a novel form of CLAD, demonstrating distinct clinical and pathological features. We aimed to further characterize the CLAD subtypes by profiling cytokine expression in bronchoalveolar lavage fluid (BALF).

Many lung transplant programs are challenged with the lifelong follow-up of recipients who reside at a distance from the transplant center. The Ontario Lung Transplant Telehealth Program aims to deliver post-transplant follow-up care to such patients through secure remote videoconferencing. Our objectives were to evaluate the feasibility and effectiveness of this service.

Introduction: Both pre-and post transplant HLA antibodies (HLAAb) in isolation have been correlated with bronchiolitis obliterans syndrome (BOS) and graft failure in lung transplant, but the temporal relationship of post transplant HLAAb to clinically relevant outcomes is not well described. Methods: We conducted a retrospective review of 98 consecutive lung transplant from 11/06 to 12/07 with 3 month survival, who had protocol post transplant HLAAb testing q3mo for one year (solid phase, Luminex TM platform).We examined the relationship of HLAAb development and presence to acute rejection (AR), diffuse alveolar damage (DAD), infections, radiographic findings, 6-minute walk, and pulmonary function tests at 3,6,9,12, and 18 months post transplant. C4d staining was not routinely performed in this cohort’s biopsies. Patients were divided into 3 groups for comparison: no HLAAb preor post-transplant (NoAb n=58), sensitized with HLAAb pre-tx (PreTxAb, n=18),and post-transplant de novo HLAAb (DNAb, n=22). The PreTxAb group received our standard high-risk protocol of perioperative plasma exchange, IVIg and MMF. Routine immunosuppression with CsA, azathioprine and prednisone was used for the remaining patients. Where appropriate, categorical variables were compared with Chi-squared or Fisher’s exact test, and continuous variables were compared using T-test, ANOVA, KruskalWallis or Rank-sum tests. Results: Of 22 DNAb, 18 developed Ab at 3-6 months and 4 at 9-12 months. 18 month survival between the three groups was not statistically different (NoAb 86.2%; PreTxAb 94.4%, DNAb 77.2%, p=NS log-rank) Immunosuppression therapy was comparable between NoAb and DNAb groups. There was no association between de novo HLAAb or pre-transplant HLAAb and AR, DAD, infection, 6 minute walk, or XR findings at any timepoint. Early de novo HLAAb, and to a lesser extent pre-transplant HLAAb, were associated with decreased FEV1 at 18 months post-transplant to <80% of best FEV1 achieved (BOS-1). (Table) After adjusting for AR and CMV infection in the first year, early DNAb remained a significant predictor of BOS at 18 months post-transplant (OR 7.68:2.28-25.8).